1-aryl-2-alkyl or-alkenyl-3,4-dihydronaphthalenes

ABSTRACT

CERTAIN 1-ARYL-2-ALKYL OR -ALKENYL-3,4-DIHYDRONAPTHALENESE, HAVING HYPOCHOLESTEREMIC AND ANTISEPTIC ACTION, ARE PREPARED VIA GRIGNARD OR ALLIED REACTIONS ON THE CORRESPONDING 1-TETRALONES.

United States Patent 3,813,430 l-ARYL-Z-ALKYL OR -ALKENYL-3,4-DIHYDRO-NAPHTHALENES Donald K. Phillips, East Greenbush, N.Y., assignor toSterling Drug Inc., New York, N.Y.

No Drawing. Filed Oct. 26, 1970, Ser. No. 84,135 Int. Cl. C07c 39/12,43/20, 69/14 US. Cl. 260-479 R 16 Claims ABSTRACT OF THE DISCLOSURECertain 1-aryl-2-alkyl or -alkenyl-3,4-dihydronaphthalenes, havinghypocholesteremic and antiseptic action, are

prepared via Grignard or allied reactions on the correspondingl-tetralones.

This invention relates to 1-aryl-2-alkyl or -alkenyl-3,4-dihydronaphthalenes and in particular is concerned with compounds of theformula wherein R is alkyl or alkenyl of from one to ten carbon atoms; Ris a member of the group consisting of hydrogen, lower-alkyl, hydroxy,lower-alkanoyloxy, hydroxylower-alkoxy, dihydroxy-lower-alkoxy andwherein Y is lower-alkylene of 2-5 carbon atoms and N=B isdi-lower-alkylamino, pyrrolidino, piperidino or morpholino; and R" is amember of the group consisting of hydroxy, lower-alkoxy,lower-alkanoyloxy, hydroxylower-alkoxy, dihydroxy-lower-alkoxy and Thegroups R and R" in the above formula I can be in any of the possiblepositions of the respective benzene rings.

In the compounds of formula I above, the alkyl or alkenyl groups R havefrom one to ten carbon atoms and may be straight or branched, thusincluding such groups as methyl, ethyl, propyl, isopropyl,tertiary-butyl, hexyl, octyl, decyl, 6-methylnonyl, vinyl, allyl,S-butenyl, 4-hexenyl, 3-decenyl, and the like.

In the compounds of formula I above, where R and/ or R" stand forlower-alkyl, lower alkoxy, hydroxy-loweralkoxy, dihydroxy-lower-alkoxyor -OYN=B where N=B is di-lower-alkylamino, the lower-alkyl moiety hasfrom one to about six carbon atoms which can be straight or branched.

In the compounds of formula I above, where R and/ or R" stand forlower-alkanoyloxy, lower-alkanoyl has from one to about six carbonatoms, thus including such groups as formyl, acetyl, propionyl, valeryl,isovaleryl, butyryl, isobutyryl, caproyl and the like.

In the compounds of formula I above, where R and/or R" stand forhydroxy-lower-alkoxy or dihydroxy-loweralkoxy, the hydroxy groups arepreferably not attached to the carbon atom adjacent to the ether oxygen,and, in the case of the dihydroXy-loWer-alkoxy groups, the two hydroxygroups are preferably attached to difierent carbon atoms.

3 ,813,430 Patented May 28, 1974 ice The compounds of formula I areprepared by interacting a compound of the formula and with a Grignardreagent R'C H.,MgX, X being halogen, preferably chlorine, bromine oriodine, and then hydrolyzing the reaction mixture. The resultingtertiary carbinol of the formula is not isolated but is dehydrated to acompound of formula I either during the work-up of the Grignard reactionor by heating in an inert solvent with a trace of a strong acid.

In the foregoing Grignard reaction it is preferred that R be hydrogen,lower-alkyl or lower-alkoxy and R" lower-alkoxy because of the readyavailablility of starting materials, although the compounds where R' ishydroxy are also readily prepared using a Grignard reagent derived fromthe 2'-tetrahydropyranyl ether or a hydroxyphenyl halide. After theGrignard reaction, the 2-tetrahydropyranyl ether is cleaved with strongacid.

The compounds of formula I where R and/or R" are lower-alkoxy arereadily converted to other compounds of formula I by conventionalmethods. The loWer-alkoxy groups are readily cleaved to hydroxy groupsby heating with pyridine hydrochloride or boron tribromide. The hydroxygroups in turn can be esterified with an acid anhydride or acid halideto form lower-alkanoyloxy groups, or etherified with the appropriatesubstituted alkyl halide to form lo-wer-alkoxy, hydroxy-lower-alkoxy,dihydroXy-lower-alkoxy, or amino-lower-alkoxy groups. If desired,similar transformations can be carried out with the group R" in thetetralone intermediate H prior to the Grignard reaction.

The intermediate tetralones of formula II are prepared by alkylation ofthe corresponding R"-l-tetralones. An R"-1-tetralone, R" preferablybeing lower-alkoxy, is heated with cyclohexylamine to give thecorresponding 1- cyclohexylimino compound, which with ethylmagnesiumbromide is converted to the N-magnesium bromide salt. The latter whentreated with an alkyl or alkenyl halide, RX, affords the desiredtetralone of formula II.

The compounds of the invention of formula I where R and/or R" are--OYN=B are basic in nature and readily form acid-addition salts. Itwill be appreciated that formula I not only represents the structuralconfiguration of the free bases but is also representative of therespective structural entity which is commonto all of the respectivecompounds of formula I whether in the form of the free bases or in theform of the acid-addition salts of the bases. By virtue of this commonstructural entity, the bases and their salts have inherent biologicalactivity of a type to be more fully described hereinbelow. When used forpharmaceutical purposes one can employ the free bases themselves or theacid-addition salts formed from pharmaceutically-acceptable acids, thatis, acids whose anions are innocuous to the animal organism in elfectivedoses of the salts so that beneficial properties inherent in the commonstructural entity represented by the free 'bases are not vitiated byside-effects ascribable to the anions.

In utilizing the pharamacodynamic activity of the salts of theinvention, pharmaceutically-acceptable salts are preferred. Althoughwater-insolubility, high toxicity, or lack of crystalline character maymake some particular salt species unsuitable or less desirable for useas such in a given pharmaceutical application, the water-insoluble ortoxic salts can be converted to any desired pharmaceutically-acceptablesalt by double decomposition reactions involving the anion, for example,by ion-exchange procedures. Moreover, apart from their usefulness inpharmaceutical applications, the salts are useful as characterizing oridentifying derivatives of the free bases or in isolation orpurification procedures.

It will be appreciated from the foregoing that all of the acid-additionsalts of the new bases of the invention are useful and valuablecompounds, regardless of considerations of solubility, toxicity,physical form, and the like, and are accordingly within the purview ofthe instant invention.

The novel feature of the compounds of the invention, then, resides inthe concept of the bases and cationic forms of the basic compounds offormula I and not in any particular acid moiety or acid anion associatedwith the salt forms of the compounds; rather, the acid moieties oranions which can be associated in the salt forms are in themselvesneither novel nor critical and therefore can be any acid anion oracid-like substance capable of salt forma tion with bases. In fact, inaqueous solutions, the base form or water-soluble acid-addition saltform of the compounds of the invention both possess a common protonatedcation or ammonium ion.

Thus the acid-addition salts discussed above and claimed herein areprepared from any organic acid, inorganic acid (including organic acidshaving an inorganic group therein), or organometallic acid asexemplified by organic monoand polycarboxylic acids. Illustrativeacid-addition salts are those derived from such diverse acids as formicacid, acetic acid, isobutyric acid, alpha-mercaptopropionic acid, malicacid, fumaric acid, succinic acid, succinamic acid, tartaric acid,citric acid, lactic acid, benzoic acid, 4-methoxybenzoic acid, phthalicacid, anthranilic acid, l-naphthalenecarboxylic acid, cinnamic acid,cyclohexanecarboxylic acid, cyclohexanesulfamic acid, mandelic acid,tropic acid, crotonic acid, acetylene dicarboxylic acid, sorbic acid,2-furancarboxylic acid, cholic acid, pyrenecarboxylic acid,2-pyridinecarboxylic acid, 3-indoleacetic acid, quinic acid, sulfamicacid, methanesulfonic acid, isethionic acid, benzenesulfonic acid,p-toluenesulfonic acid, benzenesulfinic acid, butylarsonic acid,diethylphosphinic acid, p-aminophenylarsinic acid, phenylstibnic acid,phenylphosphinous acid, methylphosphinic acid, phenylphosphinic acid,hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydriodic acid,perchloric acid, nitric acid, sulfuric acid, phosphoric acid,hydrocyanic acid, phosphotungstic acid, molybdic acid, phosphomolybdicacid, pyrophosphoric acid, arsenic acid, picn'c acid, picrolonic acid,barbituric acid, boron trifluoride, and the like.

The acid-addition salts are prepared either by dissolving the free basein an aqueous solution containing the appropriate acid and isolating thesalt by evaporating the solution, or by reacting the free base and acidin an organic solvent, in which case the salt separates directly or canbe obtained by concentration of the solution.

Biological evaluation of the compounds of formula I by standard testprocedures has shown that they possess hypocholesteremic activity andare therefore useful in the treatment or prevention of atheroscleroticconditions in mammals. The compounds were administered by stomach tubeto male rats and the serum blood cholesterol levels measured by themethod of Turner and Bales [Scand. J. Clin. Lab. Investigation 9, 210(1959)]. The compounds of the invention were generally found to beeffective in dose levels ranging from 25 to mg./kg., although certainspecies, for example, 2-hexyl-l-(p-acetoxyphenyl)-3, 4-dihydro 6methoxynaphthalene, are effective at dose levels as low as 5 mg./ kg.

Biological evaluation of the compounds of formula I by standard serialdilution procedures has shown that they also possess bacteriostatic andfungistatic activity, and are therefore useful as antiseptic agents.They have been found to be effective in vitro against such organisms asStaphylococus aureus and Trichophyton mentagrophytes at concentrationsof 25-50 ug/m1.

The actual determination of the numerical biological data definitive fora particular compound is readily obtained by standard test procedures bytechnicians trained in pharmacological test procedures, without the needfor any extensive experimentation. They are prepared for use byconventional pharmaceutical formulation procedures, that is, in capsuleor tablet form with conventional excipients (for example, calciumcarbonate, starch, lactose, talc, magnesium sterarate, gum acacia, andthe like) for oral administration; or as an aqueous or oil suspension ina pharmaceutically acceptable vehicle (aqueous alcohol, glycol, oilsolution, or oil-water emulsion) for parenteral administration. Thecompounds in suitable media can also be applied topically to organic orinorganic surfaces for disinfectant purposes.

The structures of the compounds of the invention were established by themodes of synthesis, by elementary anal ysis, and by infrared,ultraviolet and nuclear magnetic resonance spectral determinations.

The following examples will further illustrate the invention.

PREPARATION 1 (a) l-cyclohexylimino 6 methoxy 1,2,3,4tetrahydronaphthalene.-A mixture of 352.5 g. of 6-methoxye-tetralone,300 g. of cyclohexylamine, 225 ml. of toluene and 10 drops of glacialacetic acid was heated at reflux under a water separator for 24 hours.An additional 50 g. of eyclohexylamine was added and the mixture heatedfor an additional 72 hours under the water separator. The mixture wasconcentrated to remove the solvent and the residue containingl-cyclohexylimino-G-methoxy-l,2,3,4- tetrahydronaphthalene was usedwithout further purification in part (b) below.

By replacing the 6-methoxy-e-tetralone in the foregoing preparation by amolar equivalent amount of S-methoxya-tetralone, 7-methoxy-a-tetralone,8-methoxy-a-tetralone or 6-(n-butoxy)-a-tetralone, there can beobtained, respectively,

1-cyclohexylimino-5-methoxy-1,2,3,4-tetrahydronaphthalene,

1-cyclohexylimino-7-methoxy-l,2,3,4-tetrahydronaphthalene,

1-cyclohexylimino-8-methoxy-1,2,3,4-tetrahydronaphthalene,

l-cyclohexylimino-6- (n-butoxy) -l ,2, 3,4-tetrahydronaphthalene.

(b) 2 allyl 3,4-dihydro-6-methoxy-1(2H)-naphthalenone [11; R is CH CH=CHR" is 6-CI-l O].--A solution of ethylmagnesium bromide (400 ml. 3 N inether) was concentrated to remove most of the ether, and the etherreplaced by 400 ml. of tetrahydrofuran. A solution of 257 g. of thel-cyclohexylimino-6-methoxy-1,2,3,4- tetrahydronaphthalene from part (a)in 800 ml. of tetrahydrofuran was added in a fine stream to the Grignardreagent held at reflux. The mixture was stirred at reflux for 21 hours,then cooled, and 145.2 g. of allyl bromide in 200 ml. of tetrahydroflranwas added dropwise at a rate such that gentle reflux was maintained. Theresulting mixture was stirred at reflux for 22 hours, then concentratedto half its volume and filtered to remove gummy solid. Ether (3.5liters) was added to the filtrate which was again filtered andconcentrated to a residual oil (227 g.). The latter was partitionedbetween ether and dilute hydrochloric acid, and the ether layers driedover anhydrous sodium sulfate. The aqueous layers were stirred at refluxfor four hours, cooled and extracted with ether. The ether extracts weredried, combined with the ether solution obtained previously,concentrated, and distilled to give 150 g. of2-allyl-3,4-dihydro-6-methoxy-l(2H)- naphthalenone, pale yellow oil,B.P. 145-l47 C. (0.1 mm), n =1.5687.

By replacing the allyl bromide in the foregoing preparation by a molarequivalent amount of isopropyl bromide, 4-hexenyl bromide or 3-deceny1bromide, there can be obtained, respectively, 2-isopropyl-3,4-dihydro-6-methoxy-l(2H)-naphthalenone [II; R is CH(CH R" is 6 CH O]; 4hexenyl-3,4-dihydro-6-methoxy-1(2H)- naphthalenone [11; R is CH CH CHCH=CHCH R" is 6-CH O]; or 3 decenyl 3,4-dihydro-6-methoxy-l (2H)-naphthalenone [H; R is CH CH CH=CH(CH CH R" is 6CH30].

By replacing the 1-cyclohexylimino-6-methoxy-l,2,3,4-tetrahydronaphthalene in the foregoing preparation by a molar equivalentamount of l cyclohexylimino 5-methoxy 1,2,3,4 tetrahydronaphthalene, 1cyclohexylimino 7 methoxy 1,2,3,4-tetrahydronaphthalene, 1-cyclohexylimino 8 methoxy 1,2,3,4-tetrahydronaphthalene, or 1cyclohexylimino 6 |(n-butoxy)-l,2,3,4- tetrahydronaphthalene, there canbe obtained, respectively, 2 allyl3,4-dihydro-5-methoxy-l(2H)-naphthalenone [II; R is CH CH=CH R" is 7-CHO]; 2-allyl- 3,4 dihydro S-methoxy-l (2H)-naphthalenone [H; R is CHCH='CH R" is 8-CH O]; or 2-allyl-3,4-dihydro-6-(n-butoxy)-1(2H)-naphthalenone [H; R is CH CH=CH R" is 6-CH C-H CH CHO].

PREPARATION 2 2 (n butyl)-3,4-dihydro-6-methoxy-1(2H)-naphthalenone [H;R is CH CH CH CH R" is 6-CH OJ Was prepared according to the procedureof Preparation 1 but replacing the allyl bromide with 164.4 g. ofn-butyl bromide, and was obtained in the form of a pale yellow oil, B.P.154-156 C. (0.3 mm.), n =l.548O.

PREPARATION 3 2 methyl 3,4 dihydro-6-methoxy-1(2H)-naphthalenone [II; Ris CH R" is 6-CH O] was prepared according to the procedure ofPreparation 1 but replacing the allyl bromide with 151.4 g. of dimethylsulfate, and was obtained in the form of a pale yellow oil, 158 g., B.P.126-128" C. (0.05 mm.), n =1.5685.

PREPARATION 4 2 '(n hexyl) 3,4-dihydro-6-methoxy-1(2H)-naphthalenone [H;R is (CH CH R" is 6-CH O] was prepared according to the procedure ofPreparation 1 but replacing the allyl bromide with 233 g. of n-hexyliodide, and was obtained in the form of a low-melting solid, 162 g.,M.P. 335-365 C. when recrystallized from methanol.

PREPARATION 5 2 (n decyl) 3,4-dihydro-6-methoxy-l(2H)-naphthalenone [H;R is (CH )CH R" is 6-CH O] was prepared according to the procedure ofPreparation 1 but replacing the allyl bromide with 221.2 g. of n-decylbromide; also 100 mg. of potassium iodide was added prior to theaddition of the n-decyl bromide. The product was obtained in the form ofa pale yellow solid, 244 g., M.P. 61-62 C. when recrystallized frommethanol.

2 (n butyl) 3,4- dihydro-6-methoxy-1(2H)-naphthalenone can bedemethylated by heating it with pyridine hydrochloride to give2-(n-butyl)-3,4-dihydro-6-hydroxy- 1(2H)-naphthalenone [II; R is CH CHCH CH R" is 6-HO]. The latter can be acylated with acetic anhydride inthe presence of catalytic amounts of sulfuric acid to give 2 (nbutyl)-3,4-dihydro-6-acetoxy-l(2H)-naphthalenone [H; R is CH CH CH CH R"is 6-CH COO]; or with capropyl chloride to give 2-(n-butyl)-3,4-dihydro- 6-caproyloxy-1(2H)-naphthalenone [II; R is 2 (nbutyl) 3,4-dihydro-6-hydroxy-l(2H)-naphthalenone can also be caused toreact with 2-dimethylaminoethyl chloride, 4-dimethylaminobutyl chloride,2- (1 pyrrolidyl)ethyl chloride, 2(l-piperidyl)ethyl chloride, or2-(4-morpholinyl)ethyl chloride in the presence of sodium methoxide, togive, respectively,

2 (n-butyl -3,4-dihydro-6 (2-dimethylaminoethoxy)- 1(2H)-naphthalenone[H; R is CH CH CH CH R" is2-(n-butyl)-3,4-dihydro-6(4-dimethylaminobutoxy)-' l(2H)-naphthalenone[II; R is CH CH CH CH R is 6-(CH NCH CH CH CH O];

2- (n-butyl) -3 ,4-dihydro-6 [2( 1-pyrrolidyl)ethoxy]l(2H)-naphthalenone [H; R i CH CH CH CH R" is 6-(CH -NCH C-H O];

2- (Ii-butyl) -3 ,4-dihydro-6- [2- l-piperidyl ethoxy]l(2H)-naphthalenone [H; R is CH CH CH CH R" iS 0r2-(n-butyl)-3,4-dihydro-6-[2-(4-morpholinyl)ethoxy]- 1(2H)-naphthalenone[H; R is CH CH CH CH R is 6-0 (CH NCH CH O-].

EXAMPLE 1 2 allyl 1-(p-hydroxyphenyl)-3,4-dihydro-6-methoxynaphthalene[1; R is 'CH CH=CH R is 4-OH, R" is 6 CH O].To the Grignard reagentprepared from g. of 4-bromophenyl 2'-tetrahydropyranyl ether and 11 g.of magnesium turnings in 500 ml. of tetrahydrofuran was added a solutionof 65 g. of 2-allyl-3,4-dihydro-6-methoxy-l(2H)-naphthalenone:(Preparation 1b) in 200 ml. of tetrahydrofuran. The reaction mixturewas stirred at reflux for 23 hours. The solvent was then distilled ofi,the residue diluted with ether and shaken with aqueous ammonium chlorideto hydrolyze the Grignard complex. The ether layer was separated, driedover anhydrous sodium sulfate and concentrated. The residue wasredissolved in ether, extracted with 5% aqueous sodium hydroxide, washedwith water, dried over anhydrous sodium sulfate and again concentrated.The residual oil (123 g.) in 400 ml. of methanol and m1. of 3N-hydrochloric acid was stirred at reflux for 90 minutes. The residuewas dissolved in ether, washed with aqueous sodium hydroxide solution,dried over sodium sulfate, and concentrated to give 51 g. of2-allyl-l-(p-hydroxyphenyl)-3,4-dihydro-6 methoxynaphthalene as ared-brown oil. Acidification and extraction of the alkaline extractsafforded an additional 26 g. of product.

EXAMPLE 2 2-allyl-1-[p-(Z-diethylarninoethoxy)phenyl]-3,4dihydro--methoxynaphthalene [1; R is CH CH=CH R is 4- OCH CH N(C H R is6-CH O] .A mixture of 14.5 g. of 2-allyl-1-(p-hydroxyphenyl)-3,4-dihydro-6-methoxynaphthalene (Example 1), 3.8 g. ofsodium methoxide, 200 ml. of chlorobenzene and 25 ml. of methanol wasstirred and distilled until the head temperature reached C. The mixturewas cooled, 12.2 g. of Z-diethylaminoethyl chloride added, and themixture stirred at reflux for 3.5 hours. The solution was concentratedto remove the solvent, the residue dissolved in ether and the ethersolution extracted with dilute hydrochloric acid. The aqueous acidsolution was made basic with sodium hydroxide, and the alkaline mixtureextracted with ether. The ether extracts were dried over anhydroussodium sulfate and concentrated to give 20 g. of2-allyl-1-[p-(Z-diethylaminoethoxy)phcnyl]-3,4-dihydro-6-m.ethoxynaphthalene as a redbrown oil. The latter wasdissolved in ether and treated with ethereal hydrogen chloride to yielda gum. The gum was dissolved in benzene and the solution diluted withether whereupon there crystallized 21 g. of Z-allyl-l-[p-(Z- diethylaminoethoxy) phenyl] -3 ,4-dihydro-6-methoxyn aphthalene in the formof its hydrochloride salt, cream colored solid. M.P. 116-119" C. aftertwo recryst'allizations from ethyl acetate.

By replacing the 2-diethylaminoethyl chloride in the foregoing procedureby a molar equivalent amount of 4- dimethylaminobutyl bromide,2-rnethyl-3-dimethylaminopropyl chloride, Z-dihexylaminoethyl chloride,2-(l-pyrrolidyl)ethyl chloride, 2-(1-pipenidyDethyl chloride or 2-(4-morpholinyl)ethyl chloride, there can be obtained, respectively,

2-allyl-1- [p-(4-dimethylaminobutoxy) phenyl] -3,4-dihydro-6-methoxynaphthalene [1; R is CH CH=CH R is 4-OC'H CH CH CH N(C119 R is 6-CH O];

2-allyl-1-[p-(Z-methyi-3-dimethylaminopropoxy) phenyl]3,4-dihydro-6-rnethoxynaphthalene [1; R is CH CH=CH R is 4-OCH CH(CH )CHN(CH R is 6-CH O];

2-allyl-1-[p-(Z-dihexylaminoethoxy)phenyl] -3,4-dihydro-G-methoxynaphthalene [1; R is CH CH=CH R is 4-OCHZCHZN(CGHI3)Z, R" is2-allyl- 1-{ p- [2-( l-pyrrolidyl ethoxy] phenyl}-3,4-dihydro-6-methoxynaphthalene [1; R is CH CH=CH R is 4-OCH2CH2N(CH2)4, R" is2-allyl-1-{p- [2-( l-piperidyl) ethoxy] phenyl}-3,4-dihydro6-me'thoxynaphthalene [1; R is CH CH=CH R is 4-OCH CH N(CH R" is 6-CHO]; or

2-allyl-1-{p-[2-(4-morpholinyl)ethoxy]phenyl}-3,4-dihydro-6-methoxynaphthalene [1; R is CH CH=CH R is 4-OCH CH N(CH O,R" is 6-CH O].

EXAMPLE 3 Z-methyl-l-(p-hydroxyphenyl)-3,4-dihydro-6 methoxynaphthalene[1; R is CH R is 4-OH, R is 6-CH 'O] was prepared from 64.3 g. of4-bromophenyl 2-tetrahydroxypyranyl ether, 6.1 g. of magnesium and 38 g.of Z-methyl- 3,4-dihydro-6-methoxy-1(2H)-naphthaleneone (Preparation 3)according to the procedure of Example 1. The product was obtained in theform of an oil used directly in the procedure of Example 4 below.

By replacing the 2-methyl-3,4-dihydro-6-rnethoxy-1 (2H)-naphthalenone inthe foregoing preparation by a molar equivalent amount of 2-allyl-3,4-dihydro-5 -methoxy- 1 (2H) -naphthalenone,

2-allyl-3,4-dihydro-7-methoxy-1 2H) -naphthalenone,

2-allyl-3,4-dihydro-8-methoxy-1 2H -naphthalenone,

2- (n-butyl) -3,4-dihydro-6- (Z-dimethylaminoethoxy) -1 (2H)naphthalenone,

Z-(n-butyl) -3,4-dihydro-6-( 4-dimethylaminobutoxy) 1 (2H)-naphthalenone,

2-(n-butyl -3,4-dihydro-6- [2-( 1-pyrrolidyl)ethoxy]- 1( 2H-naphthalenone,

2- (n-butyl) -3,4-dihydro-6- [2 l-piperidyl) ethoxy] 1 (2H)-naphthalenone, or

2-(n-butyl) -3,4-dihydro-6- [2- l-morpholinyl) ethoxy] 1 (2H)-naphthalenone,

there can be obtained, respectively,

2-allyl- 1- (p-hydroxyphenyl -3 ,4-dihydro-5-methoxynaphthalene [1; R isCH CH=CH R is 4-OH, R" is 5-CH O'] 82-allyl-1-(p-hydroxyphenyl)-3,4-dihydro-7-methoxynaphthalene [1; R is CHCH=CH R is 4-OH, R is 7-01 1301 2-allyl-1-(p-hydroxyphenyD-3,4-dihydro-8-methoxynaphthalene [1; R is CH CH=CH R is 4-OH, R" isS'CH30]Z-(n-butyl)-1-(p-hydroxyphenyl)-3,4-dihydro-6-(2-dimethylaminoethoxy)naphthalene[1; R is CAHQ, R is 4-OH, R is 6-(CH NCH CH O];

2- (n-butyl) -l-(p-hydroxyphenyl) -3,4-dihydro-6-(4-dimethylaminobutoxy)naphthalene [1; R is C H R is 4-O-H,R" is 6-(CH NCH CH CH CH O];

2- (n-butyl) -1- p-hydroxyphenyl) -3 ,4-dihydro-6- [2-(lpyrrolidyhethoxy] -naphthalene [1; R is C H R is 4-O'H, R is 2-(n-butyl l- (p-hydroxyphenyl) -3,4-dihydro-6- [2-( 1-piperidyl)ethoxy1naphthalene [1; R is CQHQ, R is 4-OH, R is 6-(CH NCH CHO']; or

2- (n-butyl) 1 (p-hydroxyphenyl) -3 ,4-dihydro-6- 2- (4-morpholinyl)ethoxy] naphthalene [1; R is (3 1-1 R is 4-OH, R" is 6 O(CHNCH CH O]. 2-(n-butyl)-1-(p-hydroxyphenyl)-3,4-dihydro-6-(4dimethylaminobutoxy)naphthalene can be caused to react withZ-diethylaminoethyi chloride in the presence of sodium methoxideaccording to the procedude of Example 2 to give2-(n-butyl)1-[p-(2-diethylaminoethoxy)phenyl]-3,4-dihydro6-(4-dimethylarninobutoxy)naphthalene [1; R

is (1 1-1 R is 4-(C H CH CH O, R is 6- (CH NCH CH CH CH O] EXAMPLE 42-allyl-l-(p-acetoxyphenyl)-3,4-dihydro 6 methoxynaphthalene [1; R is CHCH=CH R is 4-OCOCH R" is 6-C1-I O].A mixture of 11.5 g. ofZ-methyl-l-(p-hydroxyphenyl)-3,4-dihydro 6 methoxynapthalene (Example3), 40 ml. of acetic anhydride and 3 drops of concentrated sulfuric acidwas heated on a steam bath for 75 minutes. The reaction mixture waspoured into 600 ml. of ice water, stirred for 30 minutes and thenextracted with ether. The ether extracts were washed with saturatedsodium chloride solution, dried over anhydrous sodium sulfate,decolorized with activated carbon and concentrated to dryness. Theresidue was recrystallized from methanol to give 7.5 g. of2-allyll-(p-acetoxyphenyl)-3,4- dihydro-6-methoxynaphthalene, pale creampowder, M.P. 798l C.

By replacing the acetic anhydride in the foregoing procedure by a molarequivalent amount of propionic anhydride, caproyl chloride or isovalerylchloride, there can be obtained, respectively,

2-ally1-1 p-propionoxyphenyl) -3,4-dihydro-6-methoxynaphthalene [1; R isCH CH=CH R is 4-OCOCH CH R is 6-CH O];

Z-allyll- (pmaproyloxyphenyl -3 ,4-dihydro-6-methoxynaphthalene [1; R isCH CH=CH R is 4-OCO(CH CH R is 6-01-1 01; or

Z-allyl- 1- (p-isovaleryloxyphenyl -3,4-dihydro-'6-methoxynaphthalene[1; R is CH CH=CH R is 4-OCOCH CH(CH R" is 6-CH O].

EXAMPLE 5 Z-methyl- 1- [p- 2-diethylaminoethoxy) phenyl]-3,4'-dihydro-6-methoxynaphthaiene [1; R is CH R is R is 6-CH O] wasprepared from 12 g. of 2-methyl-1-(phydroxyphenyl)-3,4-dihydro-6-methoxynaphthalene (Example 3), 12.7 g. of2-diethylaminoethyl chloride and 3.8 g. of sodium methoxide according tothe procedure of Example 2. There was obtained 9.2 g. of2-methyl-1-[p-(2- diethylaminoethoxy)phenyl} -3,4-dihydro-G-methoxynaph-9 thalene in the form of its hydrochloride salt, colorless powder, M.P.171-173" C. when recrystallized from isopropyl alcohol.

EXAMPLE 6 2-methyl-1-(p-tolyl)-3-4-dihydro 6 methoxynaphthalene [1; R isCH R is 4-CH R" is 6-CH O].A solution of 31 g. of2-methyl-3,4-dihydro-6-methoxy-l(2H)- naphthalenone (Preparation 3) in200 ml. of anhydrous benzene was added in a fine stream to refluxingGrignard reagent prepared from 46.3 g. of p-iodotoluene and 6 g. ofmagnesium in 200 ml. of anhydrous ether. The reaction mixture wasrefluxed for 20 hours, hydrolyzed with aqueous ammonium chloride andfiltered. The ether layer was separated, dried over anhydrous sodiumsulfate and concentrated to remove the solvent. The residue wasdissolved in 200 ml. of toluene, 500 mg. of p-toluenesulfonic acid addedand the solution heated at reflux azeotropically for two hours. Powderedpotassium bisulfate (2 g.) was then added and the solution heated atreflux for eight hours and then concentrated to remove the solvent. Theresidue was retreacted with Grignard reagent and the foregoing processrepeated. The product was distilled to give 27 g. ofZ-methyl-1-(p-tolyl)-3,4-dihydro-6-methoxynaphthalene, B.P. 143-145 C.(0.02 mm.), n =1.6085 1.6095.

By replacing the p-iodotoluene in the foregoing prep aration by a molarequivalent amount of 1-isobutyl-3-iodobenzene, 1-ethyl-2-iodobenzene, oriodobenzene, there can be obtained, respectively,

2-methyl-1- m-isobutylphenyl -3,4-dihydro- 6-methoxynaphthalenefl; R isCH R is 3-(CH CH(CH R" is 6-CH2-methyl-1-(o-ethylphenyl)-3,4-dihydro-6-methoxynaphthalene [I; R is CHR is 2-CH CH R" is 6-CH O]; or2-methyl-1-phenyl-3,4-dihydro-6-rnethoxynaphthalene [1; R is CH R is H,R is 6-CH O] EXAMPLE 7 Z-methyl-l- (p-tolyl) 3,4dihydro-6-hydroxynaphthalene [1; R is CH R is 4-CH R" is 6-HO].-Amixture of 16.5 g. ofZ-methyl-l-(p-tolyl)-3,4-dihydro-6-methoxynaphthalene (Example 6) and 75g. of pyridine hydrochloride was stirred at reflux under nitrogen forthree hours. The reaction mixture was cooled, partitioned between etherand water, and the neutral and phenolic material separated by extractingthe ether layer with aqueous potassium hydroxide. The alkaline extractswere acidified and the resulting Z-methyl-l-(p-tolyl)-3,4-dihydr0-6-hydroxynaphthalene isolated in the form of an oil which was useddirectly to prepare derivatives as described here inbelow.

EXAMPLE 8 Z-methyl-l-(p-tolyl)-3,4-dihydro 6 acetoxynaphthalene [1; R isCH R' is 4-CH R is 6-CH COO] was prepared from g. ofZ-methyl-1-(p-tolyl)-3,4-dihydro- 6-hydroxynaphthalene (Example 7), 40ml. of acetic anhydride and 3 drop of concentrated sulfuric acid. Themixture was stirred at room temperature for sixteen hours and worked upaccording to the procedure of Example 4 to give 6.5 g. ofZ-Inethyl-1-(p-tolyl)-3,4-dihydro-6-acetoxynaphthalene, pale creamsolid, M.P. 130-l32 C. when recrystallized from ether and frommethanolacetone.

By replacing the acetic anhydride in the foregoing preparation by amolar equivalent amount of propionic anhydride, isobutyric anhydride orcaproyl chloride, there can be obtained, respectively,

2-methyl-l-(p-tolyl)-3,4-dihydro-6-propionoxynaphthalene [1; R is CH Ris 4-CH R is 6-CH CH COO]; 2-methyl-1- (p-tolyl -3,4-dihydro-6-isobutyroxynaphthalene [I; R is CH R is 4-CH R" is 6-(CHCHOO]; or

1 0 2-methyl-1(p-tolyl)-3 ,4-dihydro-6-caproyloxynaphthalene [I; R is CHR is 4-CH R" is 6-CH (CH COO] EXAMPLE 9 Z-methyl-l-(p-tolyl) 3,4dihydro-6-(2-diethylaminoethoxy)-naphthalene [I; R is CH R is 4-CH R" is6-(C H )2CH CH O] was prepared from 15.6 g. of 2-methyl-1-(p-tolyl)-3,4-dihydro 6 hydroxynaphthalene (Example 7), 18.4 g.of 2-diethylaminoethyl chloride and 5.1 g. of sodium methoxide accordingto the procedure of Example 2, and was obtained (11 g.) in the form ofits hydrochloride salt, pale cream powder, M.P. 148-150 C. whenrecrystallized from acetone.

EXAMPLE 10 (a) 2 methyl-1-(p-methoxyphenyl)-3,4-dihydro-6-methoxynaphthalene [1; R is CH R is 4-OCHR is 6-CH O] was prepared from 38 g. of2-methyl-3,4-dihydro-6-methoxy-1(2H)-naphthalenone (Preparation 3) andthe Grignard reagent from 41 g. of p-bromoanisole according to theprocedure of Example 6, and was obtained (28.5 g.) in the form of palegray platelets, M.P. 97.5 C. when recrystallized from isopropyl alcohol.

(b) 2-methyl-1-(p-acetoxyphenyl) 3,4 dihydro-6-acetoxynaphthalene [I; Ris CH R is 4-OCOCH R" is 6-CH COOl was prepared from2-methyl-1(p-methoxyphenyl)-3,4-dihydro-6-methoxynaphthalene byrefluxing with pyridine hydrochloride and acetylation of the resultingdihydroxy compound [1; R is CH R is 4-OH, R is 6-HO with aceticanhydride according to the procedure of Examples 7 and 8, and wasobtained (8 g.) in the form of colorless needles, M.P. -12l C. whenrecrystallized from methanol and from ether.

EXAMPLE 11 (a) 2-butyl-l- (p-methoxyphenyl)-3,4-dihydro 6methoxynaphthalene [I; R is CH CH CH CH R is 4-OCI-I R is 6-CH O] wasprepared from 86 g. of butyl- 3,4 dihydro-6-methoxy-1(2H)-naphthalenone(Preparation 2) and the Grignard reagent from 93 g. of p-bromoanisoleaccording to the procedure of Example 6, and was obtained (89 g.) in theform of a pale yellow oil; B.P. 163-181 C. (0.07 mm).

(b) 2-butyl-l-(p-acetoxyphenyl) 3,4 dihydro-G-acetoxynaphthalene [I; Ris CH CH CH CH R is 4-OCOCH R is 6-CH COO] was prepared from 2- 2-butyl1 (p methoxyphenyl)-3,4-dihydro-6-methoxynaphthalene by refluxing withpyridine hydrochloride and acetylation of the resulting dihydroxycompound [I; R is CH CH CH CH R is 4-OH, R is 6-HO] with aceticanhydride according to the procedures of Examples 7 and 8, and wasobtained (5.7 g.) in the form of a yellow oil when purified by thicklayer chromatography on silica plates.

EXAMPLE 12 2-buty1-1-(p-hydroxphenyl)-3,4-dihydro 6 methoxynaphthalene[I; R is CH CH CH CH R is 4-OH, R is 6-CH O] was prepared from 81 g. of2-butyl-3,4-dihydro-6-methoxy-1(2H)-naphthalenone (Preparation 2) andthe Grignard reagent from 113 g. of p-bromophenyl 2- tetrahydropyranylether according to the procedure of Example 1, and was obtained in theform of an oil used directly to prepare derivatives as describedhereinbelow.

EXAMPLE 13 2-butyl-l-(p-acetoxyphenyl) 3,4 dihydro-6-methoxynaphthalene[1; R is CH CH CH CH R is 4-OCOCH R is 6-CH O] was prepared byacetylation of 2-butyl- 1-(p-hydroxyphenyl)-3,4-dihydro 6methoxy-naphthalene according to the procedure of Example 4, and wasobtained in the form of a straw-colored oil when purified by thick layerchromatography.

1 1 EXAMPLE 14 2butyl-l-[p-(Z-diethylaminoethoxy)phenyl]-3,4-dihydro-6-methoxynaphthalene[I; R is CH CH CH CH R is 4-OCH CH N-(C H R" is 6-CH O] was preparedfrom g. of 2-butyl-1-(p-hydroxyphenyl)-3,4-dihydro- 6-methoxynaphthalene(Example 12) and 18.4 g. of 2- diethylaminoethyl chloride according tothe procedure of Example 2, and was obtained (22 g.) in the form of itshydrochloride salt, tan powder, M.P. 120-122 C. when recrystallized fromethyl acetate.

EXAMPLE 1s 2 butyl 1-[p-(2,3-dihydroxypropoxy)phenyl]-3,4-dihydro-G-methoxynaphthalene [I; Ris CH CH CH CH R is 4-OCH CH(OH)CH OH, R" is 6-CH O].A mixture of 9.0 g.of 2-butyl-1-(p-hydroxyphenyl)-3,4-dihydro-6-methoxynaphthalene (Example12), 1.8 g. of sodium rnethoxide and 100 ml. of isoamyl alcohol wasstirred and distilled until the head temperature reached 130 C. Themixture was cooled, 3.3 g. of 3-chloro-1,3-propanediol and 100 mg. ofsodium iodide were added, and the reaction mixture stirred under refluxfor 150 minutes. The reaction mixture was concentrated to remove solventand the residue partitioned between water and ether. The ether layer wasdried over anhydrous sodium sulfate and concentrated. The residue wasdissolved in chloroform and chromatographed on thick layer silica platesdeveloped with 10% acetic acid in benzene. The band containing thedesired product was scraped off, extracted with ether, Washed withsodium bicarbonate solution, dried and concentrated in vacuo to produce2-butyl-1-[p-(2,3-dihydroxypropoxy)phenyl]3,4-dihydro-6-methoxynaphthalene in the form of a reddish brown oil.

By replacing the 3-chloro-1,2-propanediol in the foregoing preparationby a molar equivalent amount of ethylene chlorohydrin or6-chlorohexanol, there can be obtained, respectively, 2 butyl 1-[p(2-hydroxyethoxy) phenyl] 3,4 dihydro--methoxynaphthalene [1; R is CH CHCH CH R is 4-OCH CH OH, R" is 6-CH O], or Z-butyl- 1- [p-(6-hydroxyhexyloxy phenyl] -3,4-dihydro- 6-methoxyn'aphthalene [1; R isCH CH CH CH R is 4-O(CH OH, R" is 6-CH O].

EXAMPLE 16 (a) 2 decyl 1 (p-methoxyphenyl)-3,4-dihydro-6-methoxynaphthalene [I; R is (CH CH R is 4-OCH R" is 6-CH O] was preparedfrom 120 g. of 2-(n-decyl)- 3,4 dihydro-6-methoxy-1(2H)-naphthalenone(Preparation 5) and the Grignard reagent from 93.5 g. of p-brornoanisoleaccording to the procedure of Example 6, followed by dehydration of theintermediate carbinol by azeotropic reflux with 0.5 g. ofp-toluenesulfonic acid in 300 ml. of toluene. The crude product waschromatographed on silica and eluted with benzene-hexane (1:1) to giveZ-decyl-l-(p-methoxyphenyl)-3,4-dihydro-6-methoxynaphthalene as a paleyellow oil.

(1)) 2 decyl 1-(p-acetoxyphenyl)-3,4-dihydro-6-acetoxynaphthalate [1; Ris (CH CH R is 4-OCOCH R is 6-CH COO].A solution of 25 g. of borontribromide in 100 ml. of methylene dichloride was added drop Wise to astirred suspension of 26 g. of2-decyl-1-(p-methoxyphenyl)-3,4-dihydro-6-methoxynaphthalene (Example16) in 400 ml. of methylene dichloride held at ethanol- Dry Icetemperature under nitrogen. The mixture was stirred for 30 minutes,allowed to warm to room temperature and stirred 16 hours longer. Anadditional 12.5 g. of boron tribromide in ml. of methylene dichloridewas added dropwise and the reaction mixture stirred overnight. Thereaction mixture was added to water, the layers separated and theaqueous layer extracted with chloroform. The combined organic layerswere dried over anhydrous sodium sulfate, concentrated, and the residuecontaining the dihydroxy compound [1; R is (CH CH R is 4-OH, R" is 6-HO1treated with 150 ml. of acetic anhydride and 5 drops of sulfuric acid,which m'uiture was stirred 45 minutes at 0 C. and 45 minutes at roomtemperature. The product was chromatographed repeatedly on thick layerplates, developed with 20% acetic acid in benzene and eluted with ether,to give Z-decyl-l-(p-acetoxyphenyl)-3,4-dihydro-6-acetoxynaphthalene (6g.) in the form of a straw-colored oil.

EXAMPLE 17 2 decyl-1-(p-hydroxyphenyl-3,4-dihydro-6-methoxynaphthalene[1; R is (CI-l CH R is 4-OH, R" is 6- CH O] was prepared from g. of2-(n-deeyl)-3,4-dihydro 6-methoxy-l(2H)-naphthalenone (Preparation 5)and the Grignard reagent from 128.6 g. of 4-bromophenyl2'-tetrahydropyranyl ether according to the procedure of Example 1, andwas obtained in the form of a strawcolored oil (79 g.) used directly toprepare derivatives as described hereinbelow.

EXAMPLE l8 2 decyl 1-(p-acetoxyphenyl)3,4-dihydro-6-methoxynaphthalene[1; R is (CH CH R is 4-OCOCH R is 6-CH O] was prepared by acetylation of2-decyl-1-( phydroxyphenyl) 3,4-dihydro-6-methoxynaphthalene (EX- ample17) according to the procedure of Example 4, and was obtained in theform of a pale yellow oil when purified by chromatography on silica.

EXAMPLE 19 2decyl-1-{p-[2-(1-pyrrolidyl)ethoxy]phenyl}-3,4-dihydro-G-methoxynaphthalene[1; R is (CH CH R is 4-OCH CH N(CH R" is 6-CH O] was prepared from 19.6g. of 2 decyl-l-(p-hydroxyphenyl)-3,4-dihydro-6- methoxynaphthalene(Example 17) and 13.4 g. of 2-(1- pyrrolidyl)ethyl chloride according tothe procedure of Example 2, and was obtained in the form of itshydrochloride salt, pale cream waxy platelets, M.P. 123124 C. whenrecrystallized from ethyl acetate.

EXAMPLE 20 (a) 2 hexyl 1 (p-methoxyphenyl)-3,4-dihydro-6-methoxynaphthalene [1; R is (CH CH R is 4-OCH R is 6-CH O] was preparedfrom 76 g. of 2-(n-hexyl)- 3,4 dihydro-6-rnethoxyl(2H)-naphthalenone(Preparation 4) and the Grignard reagent from 75 g. of p-bromoanisoleaccording to the procedure of Example 6 and was obtained (28 g.) as apale yellow oil after chromatography on silica and elution wasbenzene-hexane (1:1).

(b) 2 hexyl l-(p-acetoxyphenyl)-3,4-dihydro-6-acetoxynaphthalene [I; Ris (CH CH R is -4OCOCH R" is 6-CH COO] was prepared from 26 g. ofZ-hexyl-l- (p-methoxyphenyl) 3,4 dihydro-6-methoxynaphthalene (part a)by demethylation wtih 25 g. of borontribromide and acetylation withacetic anhydride according to the procedure of Example 16(b). Theproduct was chromatographed repeatedly on thick plates, developed with20% acetic acid in benzene and eluted with ether to give 2- hexyl 1(p-acetoxyphenyl)-3,4-dihydro-6-acetoxynaphthalene in the form of astraw-colored oil.

EXAMPLE 21 2 hexvll-(p-hydroxyphenyl)-3,4-dihydro-6-methoxynaphthalene[1; R is (CH CH R is 4-OH, R" is 6- CHgO] was prepared from 76 g. of2-(n-hexyl)-3,4-dihydro G-methoxy-l(2H)-naphthalene (Preparation 4) andthe Grignard reagent from 103 g. of 4-bromophenyl 2- tetrahydropyranylether according to the procedure of Example 1. The product waschromatographed on silica and eluted with chloroform to give2-hexyl-l-(p-hydroxyphenyl)-3,4-dihydro-6-methoxynaphthalene in the formof an oil which was used directly to prepare derivatives as describedhereinbelow.

EXAMPLE 22 2-hexyl-l-(p-acetoxyphenyl) 3,4 dihydro-6-meth0xynaphthalene[1; R is (CH CH R is 4-OCOCH R" is 13 6-CH O] was prepared byacetylation of 27.5 g. of 2- hexyl-l-(p-hydroxyphenyl)-3,4-dihydro 6methoxynaphthalene (Example 21), and was obtained in the form of a paleyellow oil (26 g.) when purified by chromatography on silica.

EXAMPLE 23 2-hexyl 1 {p-[2-(1-pyrrolidyl)ethoxy]phenyl}-3,4-dihydro-6-methoxynaphthalene [I; R is (CH CH R' is 4-OCH CH N(CH R" is6-CH O] was prepared from 20 g. ofZ-hexyl-l-(p-hydroxyphenyl)-3,4-dihydro- 6-methoxynaphthalene (Example21) and 16 g. of 2-(1- pyrrolidy1)ethyl chloride according to theprocedure of Example 2, and was obtained in the form of itshydrochloride salt, cream platelets, M.P. 143-145 C. (17 g.) whenrecrystallized from. ethyl acetate.

I claim:

1. A compound of the formula wherein R is alkyl or alkenyl of from oneto ten carbon atoms; R is a member of the group consisting of hydrogen,lower-alkyl, hydroxy, lower-alkanoyloxy, hydroxy-lower-alkoxy, anddihydroxy-lower-alkoxy; and R" is a member of the group consisting ofhydroxy, loweralkoxy, lower-alkanoyloxy, hydroxy-lower-alkoxy, anddihydroxy-lower-alkoxy.

2. A compound according to claim 1 wherein the group R is in thepara-position of the phenyl ring, and the group R" is in the 6-positionof the naphthalene nucleus.

3. 2-alkenyl-1-(p-hydroxyphenyl) 3,4 dihydro-6- lower-alkoxynaphthalene,according to claim 2.

4. 2-allyl-1-(p-hydroxyphenyl) 3,4 dihydro-6-methoxynaphthalene,according to claim 3.

5. 2-alkyl-1-(p-hydroxyphenyl) 3,4 dihydro-6-loweralkoxynaphthalene,according to claim 2.

6. 2-alkyl-l-(p-hydroxyphenyl) 3,4 dihydro-6-hydroxynaphthalene,according to claim 2.

7. 2-allyl-1-(p-acetoxyphenyl) 3,4 dihydro-6-methoxynaphthalene,according to claim 2.

8. Z-methyl-l-(p-tolyl) 3,4 dihydro-G-acetoxynaphthalene, according toclaim 2.

9. 2-methyl 1 (p acetoxyphenyl)3,4-dihydro-6- acetoxynaphthalene,according to claim 2.

10. 2 butyl-l-(p-acetoxyphenyl) 3,4 dihydro-6- acetoxynaphthalene,according to claim 2.

11. 2-butyl-l-(p-acetoxyphenyl) 3,4 dihydro-G-mw thoxynaphthalene,according to claim 2.

12. 2-butyl 1 [p-(2,3-dihydroxypropoxy)phenyl]-3,4-dihydro-6-methoxynaphthalene, according to claim 2.

13. 2-decyl-l-(p acetoxyphenyl) 3,4 dihydro-6- acetoxynaphthalene,according to claim 2.

14. 2-decyl-l-(p-acetoxyphenyl) 3,4 dihydro-6-methoxynaphthalene,according to claim 2.

15. 2-hexyl-l-(p-acetoxyphenyl) 3,4 dihydro--methoxynaphthalene,according to claim 2.

16. 2-hexyl-1-( I-acetoxyphenyl) 3,4 dihydro-6-methoxynaphthalene,according to claim 2.

References Cited UNITED STATES PATENTS 3,567,737 3/ 1971 Lednicer260-612 3,471,565 10/ 1969 Nagata et a1. 260590 OTHER REFERENCES Fieseret al., Organic Chem. (1958), pp. 46 and 47.

Bergmann et al., Chem. Abstracts, vol. 41 (1947), pp. 6230-1.

Muller et al., Chem. Abstracts, vol. 46 (1952), pp. 3522-3.

JAMES A. PA'ITEN, Primary Examiner US. Cl. X.R.

260-2472 B, 247.5, 247.7 A, 247.7 C, 293.78, 293.88, 293.9, 326.3, 326.5R, 326.5 L, 326.5 M, 345.8, 345.9, 501.1, 501.21, 566 AB, 570.7, 590,612 R, 613 R, 619 F; 424-248, 267, 274, 311, 330

